The Auxiliary Resistant Genes of MRSA Cell Wall and their Inhibitors

Abstract

Although mecA,C genes encoded PBP2a, the extra resistant penicillin binding protein that naturally acquired low binding affinity of β-lactams contributes to the major overall resistance level in MRSA, its contribution still only accounted for 25% from the overall resistant level. Intrinsic PBPs also assist in the overall resistance level. The importance of this paper is to provide a current overview of the intrinsic auxiliary resistant genes that play a role in cell wall biosynthesis of MRSA such as peptidoglycan, teichoic acids, fatty acids, and cell division. For instance, the MurE and MurF ligases enzymes have shown to play a part in the transcription level of mecA and PBP2 genes that directly provide β-lactams resistance. FemA (factor essential for the expression of methicillin-resistant) inhibitors revealed to be highly synergetic with imipenem and restored MRSA sensitivity to β-lactams. WTA regulates the localization and activity of PBP2a and 4 that provides a high cross-linkage Peptidoglycan during the presence of β-lactams. TarS and the recent discovered TarP enzymes provides a different β-glycosylation modification to WTA which overall play a role in the virulence and resistance of MRSA. Inhibitors of tubulin protein FtsZ disturb cell wall site and formation which result in death. This paper also focuses on how the two-component sensors WalKR, VraRS, and GraRS control resistant genes that are essential for MRSA and VRSA. In the end, developing inhibitors against auxiliary resistant genes of MRSA can potentiate the activity of the existed cell wall antibiotics for better treatment.